It is the long range purpose of this project to study how various chemicals and physiological changes affect xenobiotic metabolism by the body. This laboratory has concentrated its effort on the lung as a target organ for exposure to environmental stresses. Present studies include isolation and culture of rabbit lung cell types for the purpose of studying localization of xenobiotic metabolism within the lung and toxication-detoxication mechanisms in individual cell populations. The following model enzyme systems are being set up for study of individual drug metabolism pathways in cell populations: p-xylene hydroxylation (cytochrome P-450 dependent), benzpyrene hydroxylation (cytochrome P-448 dependent), and N,N-dimethylaniline N-oxidation (cytochrome P-450 independent). Cells which have drug-metabolizing activity will be characterized and the cellular metabolic activity compared to that of microsomes prepared from lung tissue. Mechanisms of toxication and detoxication in lung cells will be studied in order to further understand the nature of this nonrespiratory function of the lung. BIBLIOGRAPHIC REFERENCE: Harper, C., James, M.O., Devereux, T.R., Patel, J., Bend, J.R., and Fouts, J.R.: Characteristics and development of drug metabolism by pulmonary microsomes. Agents and Actions 6:527-530, 1976.